A5048186584- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Renal and related cancers
- RNA modifications and cancer
- Ethics and Legal Issues in Pediatric Healthcare
- Sperm and Testicular Function
- Hedgehog Signaling Pathway Studies
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Gestational Trophoblastic Disease Studies
European Molecular Biology Laboratory
2024
University of Campania "Luigi Vanvitelli"
2016-2024
Institute of Genetics and Biophysics
2016-2022
Maternal inactivation of genes encoding components the subcortical maternal complex (SCMC) and its associated member, PADI6, generally results in early embryo lethality. In humans, SCMC gene variants were found healthy mothers children affected by multilocus imprinting disturbances (MLID). However, how controls DNA methylation required to regulate remains poorly defined. We generated a mouse line carrying Padi6 missense variant that was identified family with Beckwith–Wiedemann syndrome...
ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of on all its target sites, we performed high-throughput multi-locus analyses inbred hybrid ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, demonstrate that loss results in derepression imprinted allele multiple genes clusters. We...
Beckwith-Wiedemann syndrome (BWS) is a developmental disorder caused by dysregulation of the imprinted gene cluster chromosome 11p15.5 and often associated with loss methylation (LOM) imprinting center 2 (IC2) located in KCNQ1 intron 10. To unravel etiological mechanisms underlying these epimutations, we searched for genetic variants IC2 LOM.We looked cases showing clinical features both BWS long QT (LQTS), which variants. Pathogenic were identified genomic analysis targeted sequencing....
Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 20q13.32, respectively. In both these diseases a subset patients is affected multi-locus disturbances (MLID). several families, MLID associated with damaging variants maternal-effect genes encoding protein components subcortical maternal complex (SCMC). However, frequency, penetrance recurrence risks still...
Triploidy is one of the most common chromosome abnormalities affecting human gestation and accounts for an important fraction first-trimester miscarriages. has been demonstrated in a few cases recurrent pregnancy loss (RPL) but its molecular mechanisms are unknown. This study aims to identify genetic cause RPL associated with fetus triploidy.We investigated genomic imprinting, genotyped sequence-tagged site (STS) markers performed exome sequencing family including two sisters RPL. Moreover,...
ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA has a key role genomic imprinting, several imprinted genes are controlled by different mechanisms, and comprehensive study of relationship between DMR gene expression lacking. To address latter issue, we differentiated wild-type Zfp57-/- hybrid ESCs into neural precursor (NPCs) evaluated allelic genes. In mutant NPCs, observed...
The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children’s malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple alterations dictated chromosome copy-number variations have been recently demonstrated in adult cancers, raising question whether multiple loci were also affected WT. To address this issue, we analyzed and profiles 7 48 WT samples. results that occurred 35% cases, but they...
Abstract Background Imprinting Control Regions (ICRs) are CpG-rich sequences acquiring differential methylation in the female and male germline maintaining it a parental origin-specific manner somatic cells. Despite their expected high mutation rate due to spontaneous deamination of methylated cytosines, ICRs show conservation CpG-richness CpG-containing transcription factor binding sites mammalian species. However, little is known about mechanisms contributing maintenance density methyl...
Abstract The tripartite motif-containing protein 66 (TRIM66, also known as TIF1-delta) is a PHD-Bromo containing primarily expressed in post-meiotic male germ cells spermatids. Biophysical assays showed that TRIM66 domain binds to H3 N-terminus only when lysine 4 unmethylated. We addressed TRIM66’s role reproduction by loss-of-function genetics the mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking upregulated network of genes involved...
The tripartite motif-containing protein 66 (TRIM66, also known as TIF1-delta) is a PHD-Bromo–containing primarily expressed in post-meiotic male germ cells spermatids. Biophysical assays showed that the TRIM66 PHD-Bromodomain binds to H3 N-terminus only when lysine 4 unmethylated. We addressed TRIM66’s role reproduction by loss-of-function genetics mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking up-regulated network of genes...